Disorders of Movement, Sensation, and Mental FunctionDr. Gary Mumaugh and Dr. Bruce Simat

Context for Assessment of Dysfunction• Autonomic Nervous System (ANS) regulates homeostatic, reactive, and sensory

functionso Efferent nerves traveling out of CNSo 2 Divisions:

Parasympathetic Sympathetic

• Brain Stem regulates breathing and alertness and directs nerve connectionso Midbrain, Pons, and Medulla

• Cranial Nerves have sensory and motor functionso 12 nerves

• Motor Neurons control voluntary movement

Disease Categories in Neurology• Myopathy – muscle diseases• Myelopathy – cord compression diseases• Neuropathy – nerve diseases• Radiculopathy – nerve root compression• Plexopathy – nerve plexus compression• Encephalopathy – brain diseases

Disorders of Neuromuscular JunctionMyasthenia Gravis (MG)• Characterized by skeletal muscle weakness and malaise• Caused by an autoimmune disorder

o Antibodies are produced against acetylcholine (Ach) receptors. o Antibodies bind to the receptor and are not easily released. o Bound antibodies stimulate phagocytosis of endplate muscle membraneo Bound antibodies induce degradation of receptor channels

• Symptoms include Myasthenic crisis – acute muscle weakness resulting in inability to swallow, clear secretions, or breathe well.

Lambert-Eaton Myasthenic Syndrome (LEMS)• Similar to MG, but weakness improves with exertion• Caused by impaired release of Ach• Symptoms: Muscle weakness, dry mouth, decreased sweating, constipation• 60% of patients have lung carcinomas prior to diagnosis

Peripheral Nerve Disorders• Diffuse Polyneuropathies• Guillain-Barre Syndrome• Entrapment Syndromes• Charcot-Marie-Tooth Disease - (Peroneal Muscular Atrophy)

Diffuse Polyneuropathies• Characterized by peripheral nerve lesions• Caused by a variety of metabolic, toxic, and nutritional conditions• Symptoms include Glove-and-stocking anesthesia

o Characterized by loss of sensation in the hands and feet; loss of larger fibers leads to impaired proprioception

Neuropathy• Affects distal nerves in a glove like pattern• Paresthesias, weakness, sensory loss• Common in diabetes, RA, alcoholic abuse and B12 deficiency

Guillain-Barre Syndrome• Characterized by immune-mediated attack on sheaths of well-myelinated fibers• Typically occurs after an upper respiratory tract or flu viral infection. Idiopathic. • Symptoms: Varying degrees of weakness and tingling sensation in the legs leads to

complete paralysis. • 85% make complete recovery within 4 - 6 months

Entrapment Syndromes• Characterized by focal slowing and loss of intensity of motor and sensory signals• Causes of Peripheral nerve lesions:

o Local compression and trauma (Ex. Saturday night palsy or tardy ulnar palsy)

o Overuse, repetitive motion injury (Ex. Pronator terres syndrome)

o Combination of overuse and genetic predisposition (Ex. Carpal tunnel syndrome)

• Symptoms: Muscle wasting, eventually irreversible fibrosis

Charcot-Marie-Tooth Disease - (Peroneal Muscular Atrophy)• Heritable, autosomal dominant• Characterized by atrophy of peripheral motor and sensory neurons• Characterized by onset in late adolescence• Symptoms: Weakness and atrophy in distal muscles of the legs

Disorders of the Spinal Cord• Syringomyelia• Subacute Combined Degeneration of the Cord (Lichtheim’s disease)• Amyotrophic Lateral Sclerosis (ALS)• Spinal Muscular Atrophies of Infancy and Childhood• Friedreick’s Ataxia

Syringomyelia• A rare condition that produces a syrinx (fluid filled cavity) in the central spinal cord.

o Syrinx caused by spinal cord trauma• Cause is idiopathic • Symptoms include Shawl anesthesia - pain and temperature insensitivity in arms

and upper trunk

Subacute Combined Degeneration of the Cord (Lichtheim’s disease)• Characterized by a generalized lesion of the posterior half of the spinal cord• Usually caused by chronic alcohol abuse

Amyotrophic Lateral Sclerosis (ALS) • Also called Lou Gerhig’s disease and Motor Neuron disease• Characterized by lower motor neuron lesion and lateral scarring because of upper

motor neuron lesion• Fatal; 80% of people die within 3 years of diagnosis; no effective treatments• Caused by: Environmental toxins, slow viruses• Symptom: Excitotoxicity (destructive response of neurons to excessive stimulation)• Degenerative disease of UMN & LMN lesions• Diffusely affects upper and lower motor neurons of the cerebral cortex, brain stem,

and spinal cord (corticospinal tracts and anterior roots)• Disease leads to progressive weakness leading to respiratory failure and death• Unknown cause autoimmune disorder• Usually fatal in 1-2 years• S & S

o Weakness of hands, loss of grip, tripping, fallingo Disease begins distally and works proximallyo No sensation loss, no pain, no mental losso Difficulty speaking and swallowing, droolingo Death in 1-3 years from respiratory failure

• Diagnosis - History and muscle biopsy• Patient has normal intellectual and sensory function until death

Spinal Muscular Atrophies of Infancy and Childhood• Rare, heritable motor disorders that leave sensory capacities intact• Werdnig-Hoffman disease (floppy baby syndome)

o Onset in infancy, rapidly progresses o Symptoms: Motor degeneration, but normal intelligence and development

Friedreick’s Ataxia• Fatal motor-sensory disorder

o Chronic, average course of 15-20 yearso Half of patients diagnosed develop cardiomyopathies

• Caused by autosomal recessive disorder affecting production of frataxin • Results in mitochondrial dysfunction and free radical toxicity• Symptoms: Spinal cord is small and nerve fibers are depleted

Disorders Arising in the Basal Ganglia• Parkinson’s Disease• Huntington’s Disease

Parkinson Disease• Severe degeneration of the basal ganglia (corpus striatum) involving the

dopaminergic nigrostriatal pathwayo Parkinsonian tremoro Parkinsonian rigidityo Parkinsonian bradykinesiao Postural disturbanceso Autonomic and neuroendocrine symptomso Cognitive-affective symptomso Slow, degenerative CNS disorder

Course of disease lasts 10-20 years Affects twice as many men as women

o Caused by damage to the substantia negra Normally provides outflow pathway from basal ganglia to the cortex

and a feedback loop to the caudate and putameno Impairs flow of motor programs from the basal ganglia

Causes bradykinesia (slow movement) and difficulty initiating movement

o Loss of feedback loop expresses itself as resting tremoro Gradual loss of dopamine-producing cells

Typically idiopathico Known to result from lesion by toxins

Symptomso Muscle rigidity, bradykinesia, palsy (resting tremor), tiredness and weakness,

poor balance, dementia Degenerative disorder of the basal ganglia

o Usually in men over 50

o One million cases in USAParkinson Disease S & S Four classic symptoms:

o Resting muscle tremoro Slowness of voluntary movement –

bradykinesiao Impaired postural reflexes – simian

postureo Inability to maintain balance when

being shoved or bumped Other symptoms:

o Increased muscle tone or rigidityo Small “steppage” gaitso Frozen facial expression – “masked

face”o Handwriting changes – micrographia

Diagnosis - No classic diagnostic tests or lab studies

Treatmento Dopamine is used for the first five yearso Anticholinergic drugs, MAO inhibitors,

Symmetrylo The meds do not stop the progression, they only provide symptomatic reliefo Surgical treatment is currently experimental

Implanting cadaver or fetal basal ganglion cells

Huntington’s Disease• Characterized by dominant genetic defect on chromosome 4• Dementia consists of progressive loss of cognitive function• Massive cellular loss from caudate and putamen

o Course of disease is about 15 years• Symptoms: rapid, writhing contortions of hands, arms, face, trunk and profound

dementia• Also known as “chorea”• Autosomal dominant hereditary-degenerative disorder• Severe degeneration of the basal ganglia (caudate nucleus) and frontal cerebral

atrophyo Depletion of gamma-aminobutyric acid (GABA)

Cerebral Palsy• General term that applies to disabilities that derive from perinatal brain injury• Movement problems, sensory and cognitive impairment• CP is commonly classified based on the area of the body most affected

o Quadriplegic CP – all 4 limbs affected

o Diplegic CP – lower limbs affected more than uppero Monoplegic CP – only 1 limb affected

Demyelinating Disorders• Multiple sclerosis (MS)

o MS is a progressive, inflammatory, demyelinating disorder of the CNS

o Types• Mixed (general)• Spinal• Cerebellar

Multiple Sclerosis (MS)• Possibly caused by an interaction

between a viral illness in teen years and a genetic predisposition

• Arises through a single mechanism of lesiono Focal, chronic, progressive

• Areas of demyelination are called plaqueso Confined to white matter

• Optic neuritis is often the first symptom• Chronic exacerbation and remission

o Triggers: infection, medication, stress, fatigue

Alzheimer’s Disease• Dementia is the loss of ordered neural function• Main characteristic of Alzheimer’s is a slow progression of dementia, 5 years

o Initially only short-term storage and retrieval is affectedo Gradually well-consolidated memories are affected

• Patient experiences restlessness and wandering• Eventually patient is mute and paralyzed• Death usually comes from infection of a weakened, dehydrated patient• Atrophy

o Pyramidal cells die along with axons → loss of white matter → Gyri shrink → ventricles expand

• Severity and progression of disease due too Neurofibrillary tangleso Neurotic plaques - Senile plaques

Made up of Amyloid (starchlike) proteinso Amyloid beta protein

Directly toxic to neural tissue Triggers inflammatory response

• Familial, early and late onset• Nonhereditary (sporadic, late onset)

Alzheimer’s Disease• Theories

o Mutation for encoding amyloid precursor proteino Alteration in apolipoprotein Eo Loss of neurotransmitter stimulation of choline acetyltransferase

• Clinical manifestationso Forgetfulness, emotional upset, disorientation, confusion, lack of

concentration, decline in abstraction, problem solving, and judgment• Diagnosis is made by ruling out other causes of dementia